Sendai virus is the cause of a prevalent and disruptive indigenous respiratory infection of laboratory mice. Acute morbidity and mortality may accompany naturally-occurring Sendai virus infections depending on the genotype of the host. Chronic immunosuppression is a putative subclinical sequelae of infection but the influence of host genotype is not known. The proposed studies will seek to determine the short- and long-term immunological consequences of experimental subclinical Sendai virus infection in mice of resistant and susceptible genotypes and to determine how genetic resistance to this virus is expressed. Methods used will include measures of cellular B and T cell responses to antigenic stimulation in infected and uninfected mice, viral induction of natural killer cells, interferon and antigen-specific T and B cells in genetically resistant and susceptible mice, and virus replication in target tissues of resistant and susceptible mice. Preliminary genetics studies indicate that resistance to the lethal effects of Sendai virus infection is controlled by at least three autosomal dominant alleles whose effects are probably additive. Long-term objectives will include a more accurate determination of the number of genes involved using recombinant inbred strains of mice, their linkage to typed loci, how these individual genes are expressed, and how these genes modulate the clinical and subclinical consequences of Sendai virus infection.